(1) Field of the Invention
The invention relates to a method for stimulating the proliferation of differentiated cells belonging to the chondrogenic lineage in vitro and in vivo, as well as a composition comprising such differentiated cells and a drug for the local treatment of diseases related to the osteoarticular system.
The invention applies to the culturing of cells for therapeutic purposes, in particular the culturing of chondrocytes, with a view to the treatment of osteoarthritic lesions, as well as to drugs intended for the treatment of osteoarthritic lesions.
(2) Prior Art
The culturing of chondrocytes is currently an important issue, in particular within the framework of tissue regeneration in human and veterinary medicine. As a matter of fact, the autologous transplantation of cartilage cells into a diseased tissue is an advantageous method of treating diseases of the cartilage, e.g., such as osteoarthritis.
As a matter of fact, in order to avoid the use of an invasive method for total replacement of osteoarthritic joints, cartilage cells are taken from the patient and then cultured in vitro in a chondrocyte expansion medium, so as to be multiplied and finally re-implanted in the tissue. The portion of the joint affected by osteoarthritis is thus reconstructed and grafted onto the healthy portion.
Chondrocyte culture mediums generally comprise a base medium of the DMEM type, foetal calf serum or foetal bovine serum (FBS), and possibly other elements such as a mixture of antibiotics. The document U.S. Pat. No. 6,558,949 proposes an improved culture medium for chondrocytes comprising growth factors and in which the FBS is replaced by human serum. This medium enables the proliferation speed of the chondrocytes to be increased but does not significantly improve the proliferation rate.
Methods of improving cell proliferation have been developed in the field of cellular engineering. The document WO 01/46220, in particular, proposes the addition of small peptides, particularly oligopeptides comprising 3 to 5 amino acids, in order to increase the cellular viability of cells used for the production of antibodies or proteins of interest.
In this document, WO 01/46220, it appears that the addition of glycine monomer or diglycine to the culture medium only very slightly increases the proliferation of hybridoma cells in comparison with that obtained in a non-supplemented culture medium, whereas the addition of a tri- tetra- or pentapeptide of glycine increases cell proliferation significantly.